CHAPTER 6 - RESPIRATION

I. AN OVERVIEW OF GLUCOSE OXIDATION

A. Respiration, defined: The metabolic pathways by which organisms liberate stored energy.
Respiration, therefore, is the conversion of energy stored in starch, sugars, and lipids into more useable
forms for cellular reactions such as ATP and NADH. The conversion is - Glucose + oxygen -> carbon
dioxide + water + energy. Note that this is the same chemical equation for starting a FIRE using
glucose as the fuel. The difference is that metabolism in living systems is tightly regulated and
controlled and some of the energy is captured as high-energy chemical bonds for later use in cellular
work.
1. Glucose can be used as a source of energy for two kinds of respiration: 1) aerobic and 2)
anaerobic
a. Aerobic - requires oxygen as the terminal electron acceptor and is more efficient in that it
produces more ATP and leaves less energy unused in the final products (CO2 and H2O). The
stages of aerobic respiration are 1) Glycolysis: 6 carbon glucose is broken down into two three-carbon molecules of
pyruvate. Cell cytoplasm [Fig 6-3]
2) Krebs cycle: Pyruvate molecules are further broken down into CO2 and resulting
electrons are passed to the electron transport chain as NADH. Sme ATP is produced.
Mitochondria
3) Electron transport releases energy from electrons. Mitochondria
4) oxidative phosphorylation uses this energy to create ATP and other compounds.
Some energy is lost as heat. Mitochondria
2). Anaerobic: does not require oxygen, is less efficient, and leaves a good deal of energy
unused in the final products. Fermentation is a common type of anaerobic respiration:
Fermentation takes the end product of glycolysis (pyruvic acid) in the absence of oxygen
and converts it to ethanol or lactic acid and CO2.
II. GLYCOLYSIS: Glycolysis is the breakdown of glucose to pyruvic acid. This reaction is

common to both aerobic and anaerobic respiration

A. Getting to glucose.
1. What are some of the cellular sources of the glucose molecules that enter glycolysis? Starch,
sucrose, fructose and other sugars
2. From sucrose: Sucrose is one of the more common sugars in plants because it is easily
dissolved and transported through the vascular system. Sucrose can be split into glucose and
fructose by specific enzymes called sucrases in the cytoplasm, central vacuole, or cell wall.
3. From Starch: Because starch is a complex, branched molecule, a number of enzymes are
required to break it down.
a. Amylases break bonds between sugars
b. Starch phosphorylase cleaves a terminal glucose and adds a phosphate to it to make
glucose 1-phosphate
c. Debranching enzymes break down side branches of starches
B. Mechanisms by which ATP is synthesized
a. Substrate level phosphorylation: A phosphate is transferred from a substrate to ADP with
the aid of an enzyme.
b. Oxidative phosphorylation: Energy from electron donors (usually NADH) is used to
generate an electrochemical gradient. This gradient is used by ATP synthase (imbedded in
membranes) to convert ADP to ATP. Most ATP is made this way.
C. Glycolysis steps in the process

1. 1. Phosphorylation of glucose (hexokinase -> glucose-6-phosphate). This step requires an

input of energy from ATP
2. 2. Rearrangement of glucose to fructose (phosphoglucoisomerase -> fructose-6-phosphate)
3. 3. Phosphorylation (phosphofructokinase -> fructose 1,6-biphosphate). This requires an
input of energy
4. 4. Cleavage into 2 sugars (aldolase ->dihydroxyacetone phosphate and glyceraldehyde-3phosphate)
5. 5. Rearrangement of one of the glyceraldehyde-3-phosphate (triose phosphate isomerase ->
dihydroxyacetone phosphate ). Note: remaining steps are doubled!
6. 6. Oxidation and phosphate addition to #1 carbon; 2 NAD+ converted to NADH (triose
phosphate dehydrogenase -> 1,3-biphosphoglycerate)
7. 7. Transfer of the new phosphate to ADP to produce ATP (phosphoglyceratekinase -> 3phosphoglycerate). This is substrate-level phosphorylation. which requires an enzyme
8. 8. Movement of remaining phosphate from carbon #3 to #2 (phosphoglyceromutase -> 2phosphoglycerate)
9. 9. Dehydration to produce a C=O bond at the # 2 carbon (enolase -> PEP,
phosphoenolpyruvate)
10. 10. Remaining phosphate transferred to ADP to make ATP (pyruvate kinase -> pyruvic acid)
D. Glycolysis summary: [Fig 6-5]
1. Cellular site of the reaction: Cytoplasm
2. Number of steps in reaction: 10
3. Number of Enzymes involved in reaction: 10 (each step is catalyzed by an enzyme)
4. Chemical compound it begins with: glucose
5. Is energy required for reaction to start? Yes in the form of ATP. The process is phosphorylation.
6. Net energy harvest from each glucose molecule.
a. ATP's, number:2 net (4 generated, 2 used )
b. NADH2, number:2 which go to the mitochondria
c. Each glucose molecule produces two 3-carbon molecules of: Pyruvic acid
7. Is reaction cyclic or linear? linear
8. Is all the energy of the glucose captured in the pyruvate? No some is lost. The reaction is
inefficient (Second law of thermodynamics)
j. Summary equation: glucose + 2 NAD+ + 2ATP 2 pyruvate + 4 ATP + 2 NADH+ + 2H+
k. Is oxygen required for glycolysis: No
l. Would this reaction be temperature sensitive? Yes because enzymes are required to carry out
glycolysis and enzymes can be denatured by heat.

III. THE AEROBIC PATHWAY

A. The structure of the mitochondrion provides the key to its function
1. The mitochondrion is surrounded by a double membrane. The inner membrane is highly
folded. The folds are called cristae. The inner liquid center is called the matrix.
2. The Krebs cycle enzymes are found in the matrix.
3. The electron transport chain enzymes are found in the christae.
4. The inner membrane allows passage of pyruvate, ATP and ADP but not H+. This is the key to
harnessing H+ to make ATP

B. A preliminary step: Pyruvate enters the mitochondrion and is both oxidized and decarboxylated.
1. See Fig. 6-8b. Pyruvate is imported into the mitochondria
2. CO2 is removed and the molecule is oxidized by NAD+ to NADH + H+
3. The remaining acetyl group is attached to a very large molecule called coenzyme A.
Coenzyme A is composed of a nucleotide and a vitamin, pantothenic acid , one of the B vitamins
4. This process creates Acetyl coenzyme A which is the starting molecule for the Krebs cycle
5. Other compounds which can be converted to acetyl CoA and enter respiration sequence are
amino acids and fatty acids
C. The Krebs Cycle Oxidizes the Acetyl Groups of the Acetyl CoA Molecules [Fig 6-8]
1. Named after Sir Hans Krebs. [Also called the tricarboxylic cycle or TCA cycle]
2. Organelle reaction occurs in the mitochondria. The reaction consists of 8 steps, 7 of which
occur in the mitochondrial matrix (the inner compartment of folded membranes) and one step
(number 6) occurs in the mitochondrial membrane.
3. Steps in the cycle:
11. a. Acetyl-CoA + oxaloacetic acid citric acid : no ATP or NADH produced
12. b. Citric acid isocitric acid : no ATP or NADH produced
13. c. Isocitric acid -ketoglutaric acid: 1 NADH produced *
14. d. -ketoglutaric acid succinyl-CoA: 1 NADH produced *
15. e. succinyl-CoA succinic acid: 1 ATP produced *
16. f. succinic acid fumaric acid : 1 FADH2 produced *
17. g. fumaric acid malic acid : no ATP or NADH produced
18. h. malic acid oxaloacetic acid: 1 NADH produced *
4. Energy yield from each pyruvate molecule at end of Krebs cycle.
a. ATP's: 1 per cycle or 2 for each molecule of glucose
b. NADH: 3 NADH per cycle or 6 for each molecule of glucose
c. FADH2: 1 per cycle or two for each molecule of glucose
5. CO2 is released as a gas from the Krebs cycle and diffuses out of cells. 2 molecules of CO2 for
each pyruvate or 4 total for each glucose molecule. No oxygen is required for this reaction.
D. THE ELECTRON TRANSPORT CHAIN
You can think of this as a series of increasingly stronger magnets, each of which pulls an electron
from the previous one in the series and, in the process, transports protons from the inside of the
mitochondrion into the intermembrane space. There are at least 9 carriers in the series, and most
of them are proteins that are on or in the inner membrane. We still dont completely understand
how all this works, but we have a pretty good model. [Fig 6-10]. Note that the final electron
acceptor is oxygen.
1. Steps in the process [Fig 6-14]

19. a. FMN, in complex with a number of proteins called the NADH

dehydrogenase complex, accepts an electron from NADH in the mitochondrial
matrix and two protons (1 from NADH and 1 from the matrix)
20. b. It then moves the protons into the intermembrane space while
transferring the electron to an iron and sulfur-containing protein.
21. c. Coenzyme Q [Fig 6-13] accepts the electron from the NADH
dehydrogenase complex and shuttles them to the cytochrome b-c complex, in the
process pumping 2 more protons across the membrane.
22. d. The cytochrome b-c complex transfers the electron to cytochrome c,
again moving 2 protons across the membrane
23. e. The electrons are then shuttled to the cytochrome oxidase complex which
transfers the electrons to oxygen and pumping out another proton.
2. ATP SYNTHESIS
The proton gradient produced by energy from NADH represents a new form of potential
energy, much like water behind a dam, and it is this energy that is used to drive ATP
synthesis when these protons are passed through the membrane by ATP synthases. These
specialized molecules are embedded in the inner mitochondrial membrane, across which
oxidative phosphorylation produces the gradient.
a. The pumping of hydrogen ions into the intermembrane space creates a
chemical/electrical gradient. That gradient is used to make ATPs. [Fig 6-15,16]
b. The enzyme ATP synthase is embedded in the inner mitochondrial membrane.
c. Protons drive the phosphorylation of ADP to ATP
d. The total energy recaptured as ATP is estimated maximally as 36 ATPs but some
are lost. The average is somewhere between 21-36.
e. Total energy efficiency from a molecule of glucose is between 22%-38% (loss to
heat), about the same as harvesting gas by your car.
3. Summary of the reactions
a. Place in organelle where reaction occurs: In the membrane surrounding the matrix
(Fig 6.8)
b. Number of steps in electron transport : 9
c. Electron carriers of the electron transport: at least 9 carriers, most of which are
proteins.
d. Chemical compounds which enter electron transport: NADH from glycolysis,
conversion of pyruvate and the krebs cycle.
e. Is reaction is cyclic
f. CO2 is not required for electron transport but oxygen is required to accept
electrons.
g. The laws of thermodynamics apply to this reaction in that some energy is lost as
heat at each step
h. What is the effect of cyanide? Cyanide binds to and inhibits the cytochrome
oxidase complex thus stopping electron transport
i. Yield
1) Gylcolysis = 6 ATP
2) Pyruvate to Acetyl CoA = 6 ATP
3) Krebs cycle = 24 ATP
IV. ANAEROBIC PATHWAYS - If no oxygen is available, glycolysis can function normally for a time,
but NADH accumulates and NAD+ reserves can be eventually exhausted. It is possible, however, to
relieve the abundance of NADH by converting pyruvic acid to acetylaldehyde and then ethanol via

fermentation, an inefficient process producing little or no ATP. An alternative is to convert pyruvic acid to
lactic acid.
A. Types of anaerobic respiration (Figure 6.18)
1. Pyruvic acid --> 2-acetaldehyde--> ethanol (plants and fungi)
2. Pyruvic acid --> lactic acid (animals, bacteria and some fungi) - muscles when exercising hard
incur an oxygen deficit and produce lactic acid. The increased acidity (lower pH) reduces the
ability of muscle fibers to contract, leading to muscle fatigue
3. NAD+ is regenerated for reuse in glycolysis since electron transport is blocked by the lack of
oxygen. In this way, some energy is produced.
B. Disposition of energy
1. Some energy is stored in ATP [7% is released to 2 ATPs from gylcolysis]
2. The remainder is stored in ethanol or lactate and is unavailable to do work [inefficient]
3. Other energy dissipates as heat
a. Animal example: Heat used to maintain body temperature above ambientb. Plant example: Respiration is too slow to generate much heat but some plants do produce
heat to attract pollinators
V. OTHER TYPES OF RESPIRATION
A. Respiration of pentose sugar. (Not in book). An alternative pathway for glucose-6-phosphate (near
the beginning of glycolysis) is conversion to a series of 5-carbon sugars called the pentose phosphate
pathway. This alternative metabolism produces not NADH, but NADPH which does not go into the
electron transport chain, but rather is used directly in some reactions like amino acid synthesis and the
synthesis of ribose sugars important for DNA and RNA synthesis.
B. Respiration of lipids. Fats converted directly to acetyl CoA which is essential for transport of
NADH into the mitochondria. [Fig 6-19]
C. Respiration of Proteins. Proteins are broken down into acetyl CoA and substrates for the Krebs
cycle [Fig 6-19]
C. Cyanide-resistance respiration - Cyanide inhibits oxidative phosphorylation (electron transport) by
binding irreversibly to cytochrome oxidase, the final carrier in the chain. This is lethal to most
organisms because they cannot produce ATP. However, many plants have an alternative branch of
electron carriers that start from coenzyme Q and still end up transferring the high energy electron to
oxygen but without ATP synthesis. It produces lots of heat however, and some plants make use of this
for special functions (e.g. skunk cabbage relatives attract pollinators by using this heat to vaporize
stinky compounds).
D. Photorespiration Some plants increase their oxygen use when CO2 levels decline, a process
known as photorespiration. This interferes with photosynthesis and causes losses in the yield of many
crops.